2qfb
From Proteopedia
(New page: 200px<br /><applet load="2qfb" size="350" color="white" frame="true" align="right" spinBox="true" caption="2qfb, resolution 3.0Å" /> '''Crystal structure of ...) |
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caption="2qfb, resolution 3.0Å" /> | caption="2qfb, resolution 3.0Å" /> | ||
'''Crystal structure of the regulatory domain of human RIG-I with bound Zn'''<br /> | '''Crystal structure of the regulatory domain of human RIG-I with bound Zn'''<br /> | ||
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| + | ==Overview== | ||
| + | The ATPase RIG-I senses viral RNAs that contain 5'-triphosphates in the cytoplasm. It initiates a signaling cascade that activates innate immune response by interferon and cytokine production, providing essential antiviral protection for the host. The mode of RNA 5'-triphosphate sensing by RIG-I remains elusive. We show that the C-terminal regulatory domain RD of RIG-I binds viral RNA in a 5'-triphosphate-dependent manner and activates the RIG-I ATPase by RNA-dependent dimerization. The crystal structure of RD reveals a zinc-binding domain that is structurally related to GDP/GTP exchange factors of Rab-like GTPases. The zinc coordination site is essential for RIG-I signaling and is also conserved in MDA5 and LGP2, suggesting related RD domains in all three enzymes. Structure-guided mutagenesis identifies a positively charged groove as likely 5'-triphosphate-binding site of RIG-I. This groove is distinct in MDA5 and LGP2, raising the possibility that RD confers ligand specificity. | ||
==About this Structure== | ==About this Structure== | ||
2QFB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Sites: <scene name='pdbsite=AC1:Zn+Binding+Site+For+Residue+A+1001'>AC1</scene>, <scene name='pdbsite=AC2:Zn+Binding+Site+For+Residue+B+1002'>AC2</scene>, <scene name='pdbsite=AC3:Zn+Binding+Site+For+Residue+C+1003'>AC3</scene>, <scene name='pdbsite=AC4:Zn+Binding+Site+For+Residue+D+1004'>AC4</scene>, <scene name='pdbsite=AC5:Zn+Binding+Site+For+Residue+E+1005'>AC5</scene>, <scene name='pdbsite=AC6:Zn+Binding+Site+For+Residue+F+1006'>AC6</scene>, <scene name='pdbsite=AC7:Zn+Binding+Site+For+Residue+G+1007'>AC7</scene>, <scene name='pdbsite=AC8:Zn+Binding+Site+For+Residue+H+1008'>AC8</scene>, <scene name='pdbsite=AC9:Zn+Binding+Site+For+Residue+I+1009'>AC9</scene> and <scene name='pdbsite=BC1:Zn+Binding+Site+For+Residue+J+1010'>BC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QFB OCA]. | 2QFB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Sites: <scene name='pdbsite=AC1:Zn+Binding+Site+For+Residue+A+1001'>AC1</scene>, <scene name='pdbsite=AC2:Zn+Binding+Site+For+Residue+B+1002'>AC2</scene>, <scene name='pdbsite=AC3:Zn+Binding+Site+For+Residue+C+1003'>AC3</scene>, <scene name='pdbsite=AC4:Zn+Binding+Site+For+Residue+D+1004'>AC4</scene>, <scene name='pdbsite=AC5:Zn+Binding+Site+For+Residue+E+1005'>AC5</scene>, <scene name='pdbsite=AC6:Zn+Binding+Site+For+Residue+F+1006'>AC6</scene>, <scene name='pdbsite=AC7:Zn+Binding+Site+For+Residue+G+1007'>AC7</scene>, <scene name='pdbsite=AC8:Zn+Binding+Site+For+Residue+H+1008'>AC8</scene>, <scene name='pdbsite=AC9:Zn+Binding+Site+For+Residue+I+1009'>AC9</scene> and <scene name='pdbsite=BC1:Zn+Binding+Site+For+Residue+J+1010'>BC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QFB OCA]. | ||
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| + | ==Reference== | ||
| + | The C-Terminal Regulatory Domain Is the RNA 5'-Triphosphate Sensor of RIG-I., Cui S, Eisenacher K, Kirchhofer A, Brzozka K, Lammens A, Lammens K, Fujita T, Conzelmann KK, Krug A, Hopfner KP, Mol Cell. 2008 Feb 1;29(2):169-179. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18243112 18243112] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: zinc finger]] | [[Category: zinc finger]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:38:54 2008'' |
Revision as of 16:38, 21 February 2008
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Crystal structure of the regulatory domain of human RIG-I with bound Zn
Overview
The ATPase RIG-I senses viral RNAs that contain 5'-triphosphates in the cytoplasm. It initiates a signaling cascade that activates innate immune response by interferon and cytokine production, providing essential antiviral protection for the host. The mode of RNA 5'-triphosphate sensing by RIG-I remains elusive. We show that the C-terminal regulatory domain RD of RIG-I binds viral RNA in a 5'-triphosphate-dependent manner and activates the RIG-I ATPase by RNA-dependent dimerization. The crystal structure of RD reveals a zinc-binding domain that is structurally related to GDP/GTP exchange factors of Rab-like GTPases. The zinc coordination site is essential for RIG-I signaling and is also conserved in MDA5 and LGP2, suggesting related RD domains in all three enzymes. Structure-guided mutagenesis identifies a positively charged groove as likely 5'-triphosphate-binding site of RIG-I. This groove is distinct in MDA5 and LGP2, raising the possibility that RD confers ligand specificity.
About this Structure
2QFB is a Single protein structure of sequence from Homo sapiens with as ligand. Known structural/functional Sites: , , , , , , , , and . Full crystallographic information is available from OCA.
Reference
The C-Terminal Regulatory Domain Is the RNA 5'-Triphosphate Sensor of RIG-I., Cui S, Eisenacher K, Kirchhofer A, Brzozka K, Lammens A, Lammens K, Fujita T, Conzelmann KK, Krug A, Hopfner KP, Mol Cell. 2008 Feb 1;29(2):169-179. PMID:18243112
Page seeded by OCA on Thu Feb 21 18:38:54 2008
